Israel Medical Association Journal

The complex genetic nature of many common diseases makes the identification of the genes that predispose to these ailments a difficult task. In this review we discuss the elements that contribute to the complexity of polygenic diseases and describe an experimental strategy for disease-related gene discovery that attempts to overcome these factors. This strategy involves a population-based case-control paradigm and makes use of a highly informative, homogeneous founder population, many of whose members presently reside in Israel. The properties of single nucleotide polymorphisms, which are presently the markers of choice, are discussed, and the technologies that are currently available for SNP[1] genotyping are briefly presented.

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[1] SNP = single nucleotide polymorphism

This review summarizes the clinical, metabolic and genetic characteristics of early-onset type 2 diabetes in Mexico. Early-onset type 2 diabetes is both a clinical challenge and a public health problem. It is calculated that almost 300,000 Mexican diabetics are diagnosed between the ages of 20 and 40. The large Mexican family structure and the high prevalence of the disease provide a unique opportunity to identify the genes and the metabolic abnormalities involved in this form of the disease. In a hospital-based population, our group found that insulin deficiency was the main defect in this form of diabetes. Mutations in the HNF-1α or HNF-4α genes or autoimmunity to the beta cell were found in a small proportion of cases, leaving unexplained the majority of cases. Also discussed are the epidemiologic and therapeutic implications of early-onset type 2 diabetes, and the possible role of genetic testing for prevention.

Background: The mortality rate for cholecystectomy for acute cholecystitis in the elderly is 10% in low risk patients and increases threefold in high risk patients. Ultrasound-guided percutaneous transhepatic cholecystostomy may serve as a rapid and relatively safe tool to relieve symptoms of sepsis and decrease gallbladder distension.

Objective: To determine the safety and effectiveness of PTC[1] in the treatment of acute cholecystitis in elderly debilitated high risk patients.

Methods: The study sample included 10 patients aged 63–88 (mean 77.6 years) with clinical and sonographic signs of acute cholecystitis for more than 48 hours (fever, white blood cells > 12,000/mm³, positive Murphy sign and distended gallbladder) who underwent ultrasound guided PTC. All had severe underlying disease (coronary heart disease, renal failure, chronic obstructive pulmonary disease, and others) that places them at high risk for surgical intervention.

Results: Eight patients showed rapid regression of the clinical symptoms following PTC drainage. One patient, with bacterial endocarditis, was febrile for 5 days after catheter insertion, but with rapid resolution of the biliary colic and sepsis. One patient died from perforation of the gallbladder and small bowel. PTC catheters were withdrawn 3–25 days after the procedure, and the patients remained free of biliary symptoms. Two patients underwent successful elective cholecystectomy 3 weeks later.

Conclusion: PTC may be a safe and effective treatment for high risk elderly patients with acute cholecystitis. It can be followed by elective cholecystectomy if the underlying condition improves, as soon as the patient stabilizes and no sepsis is present, or by conservative management in high surgical-risk patients.

Background: Carcinoma of the gallbladder is diagnosed in 0.3–1.5% of all cholecystectomy specimens.

Objectives: To establish the overall rate of gallbladder carcinoma and unexpected gallbladder carcinoma based on our experience.

Methods: We retrospectively evaluated all consecutive cholecystectomies performed in our ward during a 6 year period in order to determine the incidence of gallbladder carcinoma and to identify common characteristics of this particular group of patients.

Results: Of the 1,697 cholecystectomies performed in our ward during the 6 years, gallbladder carcinoma was diagnosed in six patients (0.35%), but was not suspected prior to surgery in any of them. In accordance with the literature, the occurrence in women (5/6) was higher than in men (1/6). The mean age was 70 years (range 55–90). The most common symptom was abdominal pain; the majority (5/6) had cholelithiasis, and the pathologic report confirmed the diagnosis of adenocarcinoma in all six patients.

Conclusions: The overall incidence of unsuspected gallbladder carcinoma in our series was 0.35%. We could not find any common characteristics for this particular group of patients when compared to patients with non-malignant pathology.

Background: The role of continuous renal replacement therapy in patients with acute renal failure is well recognized. CRRT[1] has also become an important modality of treatment in various acute situations without renal failure.

Objectives: To describe our experience with CRRT in acutely ill infants and children without renal failure.

Methods: We analyzed all infants and children who underwent CRRT during the years 1998-2000 in the pediatric intensive care unit and we focus our report on those who were treated for non-renal indications.

Results: Fourteen children underwent 16 sessions of CRRT. The indications for CRRT were non-renal in 7 patients (age range 8 days to 16 years, median = 6.5). Three children were comatose from maple syrup urine disease, three were in intractable circulatory failure secondary to septic shock or systemic inflammatory response, and one had sepsis with persistent lactic acidosis and hypernatremia. Three children underwent continuous hemodiafiltration and four had continuous hemofiltration. The mean length of the procedure was 35 ± 24 hours. All patients responded to treatment within a short period (2–4 hours). No significant complications were observed. Two patients experienced mild hypothermia (34°C), one had transient hypotension and one had an occlusion of the cannula requiring replacement.

Conclusion: Our findings suggest that CRRT is a safe and simple procedure with a potential major therapeutic value for treating acute non-renal diseases in the intensive care setting.